The overall objective for this research grant is the development of more effective oncolytic drug therapy for children. Intermediate goals by which we propose to achieve this objective are by: 1. substantiation that their is generally an optimal number of drugs for combination chemotherapy. 2. identification of metabolic lesions contributing to increased response from drug combinations. 3. development of guidelines for using 2-drug combinations in "sequential multiple therapy". 4. testing for correlation between preclinical and clinical effectiveness of 2-drug combinations in "sequential multiple therapy," and 5. selection of drug combinations that utilize new oncolytic agents. Oncolytic drug combinations that interact synergistically will be identified by the increased survival of tumor inoculated mice. Metabolic lesions produced by synergistic drug combinations will be identified biochemically from the response of cell cultures or transplantable tumor cells. The results of these preclinical studies will provide a basis for studying clinical response to these drug combinations.